The chance of developing invasive breast cancer during a woman's lifetime is approximately 1 in 8 and more than 40,000 women die of metastatic disease each year. Inherent or acquired tumor drug resistance and dose-limiting toxicity limit many agents used in the treatment of invasive breast cancer. Therefore, an important goal is the development of novel non-toxic therapeutic agents that are active against this deadly disease. We have preliminary data showing that mitochondrial catalase (mCAT) reduces metastatic progression of primary breast cancer in mice, suggesting that targeting mitochondria with catalase could be a potential strategy to treat or prevent metastatic breast cancer in women. The aims of this proposal are 1) to further characterize the ability of mCAT to suppress breast cancer metastasis in mice;and 2) develop an inducible system in mice for controlling the expression of mCAT in a time and cell dependent manner. The data generated in this proposal would confirm our preliminary observations and provide the rationale for developing and/or testing clinically relevant mitochondrial-specific drug delivery systems for treating metastatic breast cancer. PUBLIC HEALTH RELEVANCE: The project is designed to determine the ability of mitochondrially targeted catalase to suppress metastatic breast cancer in mice.